8-26028641-A-G

Variant names:

• chr8-26028641-A-G
• rs17054777
• NM_022659.4:c.551+4444T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022659.4(EBF2):​c.551+4444T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,212 control chromosomes in the GnomAD database, including 1,677 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1677 hom., cov: 33)
• Consequence: EBF2 NM_022659.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132
• Publications: 1 publications found

Genes affected

EBF2 (HGNC:19090): (EBF transcription factor 2) The protein encoded by this gene belongs to the COE (Collier/Olf/EBF) family of non-basic, helix-loop-helix transcription factors that have a well conserved DNA binding domain. The COE family proteins play an important role in variety of developmental processes. Studies in mouse suggest that this gene may be involved in the differentiation of osteoblasts. [provided by RefSeq, Oct 2011]

EBF2 Gene-Disease associations (from GenCC):

• endocrine system disorder

  Inheritance: AD Classification: LIMITED Submitted by: Broad Center for Mendelian Genomics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022659.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBF2	NM_022659.4	MANE Select	c.551+4444T>C		intron	N/A	NP_073150.2	Q9HAK2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBF2	ENST00000520164.6	TSL:2 MANE Select	c.551+4444T>C		intron	N/A	ENSP00000430241.1	Q9HAK2-1
	EBF2	ENST00000965179.1		c.551+4444T>C		intron	N/A	ENSP00000635238.1
	EBF2	ENST00000901147.1		c.200+4444T>C		intron	N/A	ENSP00000571206.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19999 AN: 152094 Hom.: 1676 Cov.: 33

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0942

Gnomad OTH AF: 0.125

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.131 AC: 20013 AN: 152212 Hom.: 1677 Cov.: 33 AF XY: 0.134 AC XY: 9989 AN XY: 74426

African (AFR) AF: 0.160 AC: 6646 AN: 41526

American (AMR) AF: 0.103 AC: 1571 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 387 AN: 3468

East Asian (EAS) AF: 0.413 AC: 2135 AN: 5166

South Asian (SAS) AF: 0.170 AC: 822 AN: 4822

European-Finnish (FIN) AF: 0.155 AC: 1646 AN: 10604

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0942 AC: 6406 AN: 68000

Other (OTH) AF: 0.128 AC: 270 AN: 2116

Alfa AF: 0.0792 Hom.: 106

Bravo AF: 0.129

Asia WGS AF: 0.289 AC: 1004 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.0
DANN	Benign	0.76
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17054777; hg19: chr8-25886157;